Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear

• Type of Material: Article
• Authors: Robert C. Hurt, Emory University; Jacob C. Garrett, Emory University; Orion P. Keifer, Emory University; Andrea Linares, Nova Southeastern University; Leena Couling, Nova Southeastern University; Robert C. Speth, Nova Southeastern University; Kerry Ressler, Emory University; Paul J. Marvar, George Washington University
• Language: English
• Date: 2015-09-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
• Final Published Version (URL): http://dx.doi.org/10.1111/gbb.12235
• Title of Journal or Parent Work: Genes, Brain and Behavior
• ISSN: 1601-1848
• Volume: 14
• Issue: 7
• Start Page: 526
• End Page: 533
• Grant/Funding Information: This research project was supported by the Emory University Integrated Cellular Imaging Microscopy Core and the following sources of funding: NIH-NHLBI 113905 (R.C.S., A.L., L.C.), Nova Southeastern University President’s Faculty Development Grant (R.C.S., A.L., P.J.M.), Nova Southeastern University Cardiovascular Neuroscience Program (R.C.S., A.L., L.C.), Shared Resource Center supported by NIH-P30 CA51008 and by NCATS 8 UL1 TR000101 (R.C.S.) and NIH R00 HL107675-03 (P.J.M).
• Keywords: Amygdala; Life Sciences & Biomedicine; angiotensin II receptor type 1; PTSD; Neurosciences & Neurology; Neurosciences; PANIC-LIKE RESPONSES; DORSAL RAPHE NUCLEUS; Behavioral Sciences; fear; cardiovascular; angiotensin II; STRIA TERMINALIS; blood pressure; extinction; MEMORY CONSOLIDATION; corticotropin-releasing factor; paraventricular nucleus
• Research Categories: Psychology, Physiological; Biology, Neuroscience

Abstract

Although generally associated with cardiovascular regulation, angiotensin II receptor type 1 (AT1aR) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1aR signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1aR gene from its CRF-releasing cells (CRF-AT1aR(−/−)). These mice exhibit normal baseline heart rate, blood pressure, anxiety, and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1aR(−/−) mice exhibit less freezing than wild type mice during tests of conditioned fear expression—an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1R activity in CRF-expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1R antagonists may act to modulate fear extinction.